Overexpression of T-LAK cell-originated protein kinase predicts poor prognosis in patients with stage I lung adenocarcinoma
Resource
Cancer Sci., 103(4), 731-738
Journal
Cancer Science
Pages
731-738
Date Issued
2012
Date
2012
Author(s)
Wei D.-C.
Yeh Y.-C.
Hung J.-J.
Chou T.-Y.
Wu Y.-C.
Lu P.-J.
Cheng H.-C.
Hsu Y.-L.
Kuo Y.-L.
Lai J.-M.
Abstract
Tumor recurrence is the most common cause of disease failure after surgical resection in early-stage lung adenocarcinoma. Identification of clinically relevant prognostic markers could help to predict patients with high risk of disease recurrence. A meta-analysis of available lung adenocarcinoma microarray datasets revealed that T-LAK cell-originated protein kinase (TOPK), a serine/threonine protein kinase, is overexpressed in lung cancer. Using stable cell lines with overexpression or knockdown of TOPK, we have shown that TOPK can promote cell migration, invasion, and clonogenic activity in lung cancer cells, suggesting its crucial role in lung tumorigenesis. To evaluate the prognostic value of TOPK expression in resected stage I lung adenocarcinoma, a retrospective analysis of 203 patients diagnosed with pathological stage I lung adenocarcinoma was carried out to examine the expression of TOPK by immunohistochemistry (IHC). The prognostic significance of TOPK overexpression was examined. Overexpression of TOPK (IHC score >3) was detected in 67.0% of patients, and these patients were more frequently characterized with disease recurrence and angiolymphatic invasion. Using multivariate analysis, patient age (>65 years old; P = 0.002) and TOPK overexpression (IHC score >3; P < 0.001) significantly predicted a shortened overall survival. Moreover, TOPK overexpression (IHC score >3; P = 0.005) also significantly predicted a reduced time to recurrence in the patients. Our results indicate that overexpression of TOPK could predetermine the metastatic capability of tumors and could serve as a significant prognostic predictor of shortened overall survival and time to recurrence. (Cancer Sci 2012; 103: 731738)
SDGs
Other Subjects
protein serine threonine kinase; T LAK cell originated protein kinase; unclassified drug; adult; aged; article; cancer cell culture; cancer prognosis; cancer staging; cancer survival; cell invasion; cell migration; clonogenesis; female; human; immunohistochemistry; lung adenocarcinoma; lung carcinogenesis; major clinical study; male; prediction; priority journal; protein expression; retrospective study; survival time; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Female; Humans; Killer Cells, Lymphokine-Activated; Lung Neoplasms; Male; Middle Aged; Prognosis; Protein-Serine-Threonine Kinases; Recurrence; T-Lymphocytes; Tumor Markers, Biological
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